Hamster cells are resistant to infection by most retroviruses including Moloney murine leukemia virus (MoMLV), and gibbon ape leukemia viruses (GaLVs). We have constructed GaLV/MoMLV hybrid recombinant virions to identify viral and cellular determinants responsible for the inability of GaLV and MoMLV to infect hamster cells. The substitution of MoMLV core components for GaLV core components circumvents the resistance of hamster cells to infection by GaLV, demonstrating that hamster cells have receptors for GaLV but are not efficiently infected by this primate retrovirus due to a post-penetration block. In contrast, the resistance of hamster cells to MoMLV infection is apparently due to the presence of a nonfunctional viral MoMLV receptor. Treatment of CHO K1 or BHK 21 cells with the glycosylation inhibitor tunicamycin allows these cells to be infected by MoMLV. The construction of recombinant MoMLV/GaLV hybrid virions that can efficiently infect resistant cells has allowed the identification of viral and cellular factors responsible for restricting productive infection of hamster cells by MoMLV and GaLV suggest specific chemical and genetic modifications of target cells that facilitate MoMLV infection.